US2024150848A1PendingUtilityA1
Methods and systems for diagnosis, classification, and treatment of small cell lung cancer and other high-grade neuroendocrine carcinomas
Est. expiryMar 3, 2041(~14.6 yrs left)· nominal 20-yr term from priority
C12Q 1/6886C12Q 2600/106C12Q 2600/154A61P 35/00
47
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Claims
Abstract
Aspects of the disclosure are directed to methods and systems for diagnosis, classification, and treatment of small cell lung cancer and high grade neuroendocrine carcinomas. Certain aspects comprise detection and analysis of tumor DNA methylation. Included in the disclosure are methods for identifying a subject as having a particular small cell lung cancer subtype based on DNA N methylation analysis, as well as methods and compositions for treatment of a subject based on subtype classification.
Claims
exact text as granted — not AI-modifiedWhat is claimed:
1 . A method of treating a subject for small cell lung cancer (SCLC), the method comprising administering a BCL2 inhibitor or a DLL3-targeted therapy to a subject having tumor DNA with differential methylation at one or more methylation sites selected from the methyation sites of Table 2, Table 7, Table 15, Table 20, and Table 27 compared to a reference or control sample.
2 . The method of claim 1 , wherein the one or more methylation sites are 2 or more methylation sites selected from the methyation sites of Table 2, Table 7, Table 15, Table 20, and Table 27.
3 . The method of claim 1 , wherein the one or more methylation sites are 3 or more methylation sites selected from the methyation sites of Table 2, Table 7, Table 15, Table 20, and Table 27.
4 . The method of claim 1 , wherein the one or more methylation sites are 4 or more methylation sites selected from the methyation sites of Table 2, Table 7, Table 15, Table 20, and Table 27.
5 . The method of claim 1 , wherein the one or more methylation sites are 5 or more methylation sites selected from the methyation sites of Table 2, Table 7, Table 15, Table 20, and Table 27.
6 . The method of claim 1 , wherein the one or more methylation sites are 10 or more methylation sites selected from the methyation sites of Table 2, Table 7, Table 15, Table 20, and Table 27.
7 . The method of claim 1 , wherein the one or more methylation sites are twenty or more methylation sites selected from the methyation sites of Table 2, Table 7, Table 15, Table 20, and Table 27.
8 . The method of claim 1 , wherein the one or more methylation sites are fifty or more methylation sites selected from the methyation sites of Table 2, Table 7, Table 15, Table 20, and Table 27.
9 . The method of claim 1 , wherein the one or more methylation sites are one or more methylation sites of Table 2.
10 . The method of claim 1 , wherein the one or more methylation sites are 2 or more methylation sites of Table 2.
11 . The method of claim 1 , wherein the one or more methylation sites are 3 or more methylation sites of Table 2.
12 . The method of claim 1 , wherein the one or more methylation sites are 4 or more methylation sites of Table 2.
13 . The method of claim 1 , wherein the one or more methylation sites are 5 or more methylation sites of Table 2.
14 . The method of claim 1 , wherein the one or more methylation sites are 10 or more methylation sites of Table 2.
15 . The method of claim 1 , wherein the one or more methylation sites are all of the methylation sites of Table 2.
16 . The method of claim 1 , wherein the one or more methylation sites are one or more methylation sites of Table 7.
17 . The method of claim 1 , wherein the one or more methylation sites are 2 or more methylation sites of Table 7.
18 . The method of claim 1 , wherein the one or more methylation sites are 3 or more methylation sites of Table 7.
19 . The method of claim 1 , wherein the one or more methylation sites are 4 or more methylation sites of Table 7.
20 . The method of claim 1 , wherein the one or more methylation sites are one or more methylation sites of Table 7.
21 . The method of claim 1 , wherein the one or more methylation sites are 10 or more methylation sites of Table 7.
22 . The method of claim 1 , wherein the one or more methylation sites are all of the methylation sites of Table 7.
23 . The method of claim 1 , wherein the one or more methylation sites are one or more methylation sites of Table 15.
24 . The method of claim 1 , wherein the one or more methylation sites are 2 or more methylation sites of Table 15.
25 . The method of claim 1 , wherein the one or more methylation sites are 3 or more methylation sites of Table 15.
26 . The method of claim 1 , wherein the one or more methylation sites are 4 or more methylation sites of Table 15.
27 . The method of claim 1 , wherein the one or more methylation sites are 5 or more methylation sites of Table 15.
28 . The method of claim 1 , wherein the one or more methylation sites are 10 or more methylation sites of Table 15.
29 . The method of claim 1 , wherein the one or more methylation sites are all of the methylation sites of Table 15.
30 . The method of claim 1 , wherein the one or more methylation sites are one or more methylation sites of Table 20.
31 . The method of claim 1 , wherein the one or more methylation sites are 2 or more methylation sites of Table 20.
32 . The method of claim 1 , wherein the one or more methylation sites are 3 or more methylation sites of Table 20.
33 . The method of claim 1 , wherein the one or more methylation sites are 4 or more methylation sites of Table 20.
34 . The method of claim 1 , wherein the one or more methylation sites are 5 or more methylation sites of Table 20.
35 . The method of claim 1 , wherein the one or more methylation sites are 10 or more methylation sites of Table 20.
36 . The method of claim 1 , wherein the one or more methylation sites are all of the methylation sites of Table 20.
37 . The method of claim 1 , wherein the one or more methylation sites are one or more methylation sites of Table 27.
38 . The method of claim 1 , wherein the one or more methylation sites are 2 or more methylation sites of Table 27.
39 . The method of claim 1 , wherein the one or more methylation sites are 3 or more methylation sites of Table 27.
40 . The method of claim 1 , wherein the one or more methylation sites are 4 or more methylation sites of Table 27.
41 . The method of claim 1 , wherein the one or more methylation sites are 5 or more methylation sites of Table 27.
42 . The method of claim 1 , wherein the one or more methylation sites are 10 or more methylation sites of Table 27.
43 . The method of claim 1 , wherein the one or more methylation sites are all of the methylation sites of Table 27.
44 . The method of any of claims 1 - 43 , wherein the tumor DNA is ctDNA.
45 . The method of any of claims 1 - 22 , wherein the method comprises administering to the subject the BCL2 inhibitor.
46 . The method of claim 45 , wherein the BCL2 inhibitor is ABT-737 or navitoclax.
47 . The method of any of claims 1 - 45 , wherein the method comprises administering to the subject the DLL3-targeted therapeutic.
48 . The method of claim 47 , wherein the DLL3-targeted therapeutic comprises an anti-DLL3 antibody or fragment thereof.
49 . The method of claim 48 , wherein the anti-DLL3 antibody or fragment thereof is rovalpituzumab.
50 . The method of claim 47 , wherein the DLL3-targeted therapeutic is an antibody-drug conjugate.
51 . The method of claim 50 , wherein the antibody-drug conjugate is rovalpituzumab tesirine.
52 . The method of claim 47 , wherein the DLL3-targeted therapeutic is a DLL3-targeted cellular therapy.
53 . The method of claim 52 , wherein the DLL3-targeted cellular therapy is a DLL3-targeted chimeric antigen receptor T-cell.
54 . The method of any of claims 1 - 52 , further comprising administering to the subject an additional cancer therapy.
55 . The method of claim 54 , wherein the additional cancer therapy comprises chemotherapy, radiotherapy, immunotherapy, or a combination thereof.
56 . The method of any of claims 1 - 55 , wherein the subject was previously treated for SCLC.
57 . The method of claim 1 - 56 , wherein the subject was resistant to the previous treatment.
58 . The method of any of claims 1 - 57 , wherein the subject was determined to have SCLC-A based on the analysis of the tumor DNA.
59 . The method of any of claims 1 - 58 , wherein the subject was further determined, from the analysis of the tumor DNA from the subject, to have differential methylation of one or more methylation sites of Table 13 compared to the reference or control sample.
60 . The method of any of claims 1 - 59 , wherein the reference or control sample is a DNA sample obtained from healthy cells from the subject.
61 . The method of any of claims 1 - 59 , wherein the reference or control sample is a DNA sample obtained from healthy cells from a reference subject.
62 . A method of treating a subject for SCLC, the method comprising administering an AURK inhibitor to a subject having tumor DNA with differential methylation at one or more methylation sites selected from the methylation sites of Table 3, Table 8, Table 16, Table 21, and Table 28 compared to a reference or control sample.
63 . The method of claim 62 , wherein the one or more methylation sites are 2 or more methylation sites selected from the methyation sites of Table 3, Table 8, Table 16, Table 21, and Table 28.
64 . The method of claim 62 , wherein the one or more methylation sites are 3 or more methylation sites selected from the methyation sites of Table 3, Table 8, Table 16, Table 21, and Table 28.
65 . The method of claim 62 , wherein the one or more methylation sites are 4 or more methylation sites selected from the methyation sites of Table 3, Table 8, Table 16, Table 21, and Table 28.
66 . The method of claim 62 , wherein the one or more methylation sites are 5 or more methylation sites selected from the methyation sites of Table 3, Table 8, Table 16, Table 21, and Table 28.
67 . The method of claim 62 , wherein the one or more methylation sites are 10 or more methylation sites selected from the methyation sites of Table 3, Table 8, Table 16, Table 21, and Table 28.
68 . The method of claim 62 , wherein the one or more methylation sites are twenty or more methylation sites selected from the methyation sites of Table 3, Table 8, Table 16, Table 21, and Table 28.
69 . The method of claim 62 , wherein the one or more methylation sites are fifty or more methylation sites selected from the methyation sites of Table 3, Table 8, Table 16, Table 21, and Table 28.
70 . The method of claim 62 , wherein the one or more methylation sites are one or more methylation sites of Table 3.
71 . The method of claim 62 , wherein the one or more methylation sites are 2 or more methylation sites of Table 3.
72 . The method of claim 62 , wherein the one or more methylation sites are 3 or more methylation sites of Table 3.
73 . The method of claim 62 , wherein the one or more methylation sites are 4 or more methylation sites of Table 3.
74 . The method of claim 62 , wherein the one or more methylation sites are 5 or more methylation sites of Table 3.
75 . The method of claim 62 , wherein the one or more methylation sites are 10 or more methylation sites of Table 3.
76 . The method of claim 62 , wherein the one or more methylation sites are all of the methylation sites of Table 3.
77 . The method of claim 62 , wherein the one or more methylation sites are one or more methylation sites of Table 8.
78 . The method of claim 62 , wherein the one or more methylation sites are 2 or more methylation sites of Table 8.
79 . The method of claim 62 , wherein the one or more methylation sites are 3 or more methylation sites of Table 8.
80 . The method of claim 62 , wherein the one or more methylation sites are 4 or more methylation sites of Table 8.
81 . The method of claim 62 , wherein the one or more methylation sites are 5 or more methylation sites of Table 8.
82 . The method of claim 62 , wherein the one or more methylation sites are 10 or more methylation sites of Table 8.
83 . The method of claim 62 , wherein the one or more methylation sites are all of the methylation sites of Table 8.
84 . The method of claim 62 , wherein the one or more methylation sites are one or more methylation sites of Table 16.
85 . The method of claim 62 , wherein the one or more methylation sites are 2 or more methylation sites of Table 16.
86 . The method of claim 62 , wherein the one or more methylation sites are 3 or more methylation sites of Table 16.
87 . The method of claim 62 , wherein the one or more methylation sites are 4 or more methylation sites of Table 16.
88 . The method of claim 62 , wherein the one or more methylation sites are 5 or more methylation sites of Table 16.
89 . The method of claim 62 , wherein the one or more methylation sites are 10 or more methylation sites of Table 16.
90 . The method of claim 62 , wherein the one or more methylation sites are all of the methylation sites of Table 16.
91 . The method of claim 62 , wherein the one or more methylation sites are one or more methylation sites of Table 21.
92 . The method of claim 62 , wherein the one or more methylation sites are 2 or more methylation sites of Table 21.
93 . The method of claim 62 , wherein the one or more methylation sites are 3 or more methylation sites of Table 21.
94 . The method of claim 62 , wherein the one or more methylation sites are 4 or more methylation sites of Table 21.
95 . The method of claim 62 , wherein the one or more methylation sites are 5 or more methylation sites of Table 21.
96 . The method of claim 62 , wherein the one or more methylation sites are 10 or more methylation sites of Table 21.
97 . The method of claim 62 , wherein the one or more methylation sites are all of the methylation sites of Table 21.
98 . The method of claim 62 , wherein the one or more methylation sites are one or more methylation sites of Table 28.
99 . The method of claim 62 , wherein the one or more methylation sites are 2 or more methylation sites of Table 28.
100 . The method of claim 62 , wherein the one or more methylation sites are 3 or more methylation sites of Table 28.
101 . The method of claim 62 , wherein the one or more methylation sites are 4 or more methylation sites of Table 28.
102 . The method of claim 62 , wherein the one or more methylation sites are 5 or more methylation sites of Table 28.
103 . The method of claim 62 , wherein the one or more methylation sites are 10 or more methylation sites of Table 28.
104 . The method of claim 62 , wherein the one or more methylation sites are all of the methylation sites of Table 28.
105 . The method of any of claims 62 - 104 , wherein the tumor DNA is ctDNA.
106 . The method of any of claims 62 - 105 , wherein the AURK inhibitor is CYC-116, alisertib, or AS-703569.
107 . The method of any of claims 62 - 106 , further comprising administering to the subject an additional cancer therapy.
108 . The method of claim 107 , wherein the additional cancer therapy comprises chemotherapy, radiotherapy, immunotherapy, or a combination thereof.
109 . The method of any of claims 62 - 108 , wherein the subject was previously treated for SCLC.
110 . The method of claim 109 , wherein the subject was resistant to the previous treatment.
111 . The method of any of claims 62 - 110 , wherein the subject was determined to have SCLC-N based on the analysis of the tumor DNA.
112 . The method of any of claims 62 - 111 , wherein the subject was further determined, from the analysis of the tumor DNA from the subject, to have differential methylation of one or more methylation sites of Table 13 compared to the reference or control sample.
113 . The method of any of claims 62 - 112 , wherein the reference or control sample is a DNA sample obtained from healthy cells from the subject.
114 . The method of any of claims 62 - 112 , wherein the reference or control sample is a DNA sample obtained from healthy cells from a reference subject.
115 . A method of treating a subject for SCLC, the method comprising administering a platinum-based chemotherapeutic agent, a PARP inhibitor, an anti-metabolite, or a nucleoside analog to a subject having tumor DNA with differential methylation at one or more methylation sites selected from the methylation sites of Table 4, Table 9, Table 17, Table 22, and Table 29 compared to a reference or control sample.
116 . The method of claim 115 , wherein the one or more methylation sites are 2 or more methylation sites selected from the methyation sites of Table 4, Table 9, Table 17, Table 22, and Table 29.
117 . The method of claim 115 , wherein the one or more methylation sites are 3 or more methylation sites selected from the methyation sites of Table 4, Table 9, Table 17, Table 22, and Table 29.
118 . The method of claim 115 , wherein the one or more methylation sites are 4 or more methylation sites selected from the methyation sites of Table 4, Table 9, Table 17, Table 22, and Table 29.
119 . The method of claim 115 , wherein the one or more methylation sites are 5 or more methylation sites selected from the methyation sites of Table 4, Table 9, Table 17, Table 22, and Table 29.
120 . The method of claim 115 , wherein the one or more methylation sites are 10 or more methylation sites selected from the methyation sites of Table 4, Table 9, Table 17, Table 22, and Table 29.
121 . The method of claim 115 , wherein the one or more methylation sites are twenty or more methylation sites selected from the methyation sites of Table 4, Table 9, Table 17, Table 22, and Table 29.
122 . The method of claim 115 , wherein the one or more methylation sites are fifty or more methylation sites selected from the methyation sites of Table 4, Table 9, Table 17, Table 22, and Table 29.
123 . The method of claim 115 , wherein the one or more methylation sites are one or more methylation sites of Table 4.
124 . The method of claim 115 , wherein the one or more methylation sites are 2 or more methylation sites of Table 4.
125 . The method of claim 115 , wherein the one or more methylation sites are 3 or more methylation sites of Table 4.
126 . The method of claim 115 , wherein the one or more methylation sites are 4 or more methylation sites of Table 4.
127 . The method of claim 115 , wherein the one or more methylation sites are 5 or more methylation sites of Table 4.
128 . The method of claim 115 , wherein the one or more methylation sites are 10 or more methylation sites of Table 4.
129 . The method of claim 115 , wherein the one or more methylation sites are all of the methylation sites of Table 4.
130 . The method of claim 115 , wherein the one or more methylation sites are one or more methylation sites of Table 9.
131 . The method of claim 115 , wherein the one or more methylation sites are 2 or more methylation sites of Table 9.
132 . The method of claim 115 , wherein the one or more methylation sites are 3 or more methylation sites of Table 9.
133 . The method of claim 115 , wherein the one or more methylation sites are 4 or more methylation sites of Table 9.
134 . The method of claim 115 , wherein the one or more methylation sites are 5 or more methylation sites of Table 9.
135 . The method of claim 115 , wherein the one or more methylation sites are 10 or more methylation sites of Table 9.
136 . The method of claim 115 , wherein the one or more methylation sites are all of the methylation sites of Table 9.
137 . The method of claim 115 , wherein the one or more methylation sites are one or more methylation sites of Table 17.
138 . The method of claim 115 , wherein the one or more methylation sites are 2 or more methylation sites of Table 17.
139 . The method of claim 115 , wherein the one or more methylation sites are 3 or more methylation sites of Table 17.
140 . The method of claim 115 , wherein the one or more methylation sites are 4 or more methylation sites of Table 17.
141 . The method of claim 115 , wherein the one or more methylation sites are 5 or more methylation sites of Table 17.
142 . The method of claim 115 , wherein the one or more methylation sites are 10 or more methylation sites of Table 17.
143 . The method of claim 115 , wherein the one or more methylation sites are all of the methylation sites of Table 17.
144 . The method of claim 115 , wherein the one or more methylation sites are one or more methylation sites of Table 22.
145 . The method of claim 115 , wherein the one or more methylation sites are 2 or more methylation sites of Table 22.
146 . The method of claim 115 , wherein the one or more methylation sites are 3 or more methylation sites of Table 22.
147 . The method of claim 115 , wherein the one or more methylation sites are 4 or more methylation sites of Table 22.
148 . The method of claim 115 , wherein the one or more methylation sites are 5 or more methylation sites of Table 22.
149 . The method of claim 115 , wherein the one or more methylation sites are 10 or more methylation sites of Table 22.
150 . The method of claim 115 , wherein the one or more methylation sites are all of the methylation sites of Table 22.
151 . The method of claim 115 , wherein the one or more methylation sites are one or more methylation sites of Table 29.
152 . The method of claim 115 , wherein the one or more methylation sites are 2 or more methylation sites of Table 29.
153 . The method of claim 115 , wherein the one or more methylation sites are 3 or more methylation sites of Table 29.
154 . The method of claim 115 , wherein the one or more methylation sites are 4 or more methylation sites of Table 29.
155 . The method of claim 115 , wherein the one or more methylation sites are 5 or more methylation sites of Table 29.
156 . The method of claim 115 , wherein the one or more methylation sites are 10 or more methylation sites of Table 29.
157 . The method of claim 115 , wherein the one or more methylation sites are all of the methylation sites of Table 29.
158 . The method of any of claims 115 - 157 , wherein the tumor DNA is ctDNA.
159 . The method of any of claims 115 - 136 , wherein the method comprises administering to the subject the platinum-containing chemotherapeutic agent.
160 . The method of claim 159 , wherein the platinum-containing chemotherapeutic agent is cisplatin, carboplatin, oxaliplatin, nedaplatin, picoplatin, or satraplatin.
161 . The method of any of claims 115 - 136 , wherein the method comprises administering to the subject the PARP inhibitor.
162 . The method of claim 161 , wherein the PARP inhibitor is talazoparib, olaparib, niraparib, AZD-2461, or rucaparib.
163 . The method of any of claims 115 - 136 , wherein the method comprises administering to the subject the anti-metabolite.
164 . The method of claim 163 , wherein the anti-metabolite is pemetrexed, methotrexate, or pralatrexate.
165 . The method of any of claims 115 - 136 , wherein the method comprises administering to the subject the nucleoside analog.
166 . The method of claim 165 , wherein the nucleoside analog is floxuridine, cytarabine, clofarabine, or fludarabine.
167 . The method of any of claims 115 - 166 , further comprising administering to the subject an additional cancer therapy.
168 . The method of claim 167 , wherein the additional cancer therapy comprises chemotherapy, radiotherapy, immunotherapy, or a combination thereof.
169 . The method of any of claims 115 - 168 , wherein the subject was previously treated for SCLC.
170 . The method of claim 169 , wherein the subject was resistant to the previous treatment.
171 . The method of any of claims 115 - 170 , wherein the subject was determined to have SCLC-N based on the analysis of the tumor DNA.
172 . The method of any of claims 115 - 171 , wherein the subject was further determined, from the analysis of the tumor DNA from the subject, to have differential methylation of one or more methylation sites of Table 13 compared to the reference or control sample.
173 . The method of any of claims 115 - 172 , wherein the reference or control sample is a DNA sample obtained from healthy cells from the subject.
174 . The method of any of claims 115 - 172 , wherein the reference or control sample is a DNA sample obtained from healthy cells from a reference subject.
175 . A method of treating a subject for SCLC, the method comprising administering an immunotherapy to a subject having tumor DNA with differential methylation at one or more methylation sites selected from the methylation sites of Table 5, Table 10, Table 18, Table 23, and Table 30 compared to a reference or control sample.
176 . The method of claim 175 , wherein the one or more methylation sites are 2 or more methylation sites selected from the methyation sites of Table 5, Table 10, Table 18, Table 23, and Table 30.
177 . The method of claim 175 , wherein the one or more methylation sites are 3 or more methylation sites selected from the methyation sites of Table 5, Table 10, Table 18, Table 23, and Table 30.
178 . The method of claim 175 , wherein the one or more methylation sites are 4 or more methylation sites selected from the methyation sites of Table 5, Table 10, Table 18, Table 23, and Table 30.
179 . The method of claim 175 , wherein the one or more methylation sites are 5 or more methylation sites selected from the methyation sites of Table 5, Table 10, Table 18, Table 23, and Table 30.
180 . The method of claim 175 , wherein the one or more methylation sites are 5 or more methylation sites selected from the methyation sites of Table 5, Table 10, Table 18, Table 23, and Table 30.
181 . The method of claim 175 , wherein the one or more methylation sites are 10 or more methylation sites selected from the methyation sites of Table 5, Table 10, Table 18, Table 23, and Table 30.
182 . The method of claim 175 , wherein the one or more methylation sites are twenty or more methylation sites selected from the methyation sites of Table 5, Table 10, Table 18, Table 23, and Table 30.
183 . The method of claim 175 , wherein the one or more methylation sites are fifty or more methylation sites selected from the methyation sites of Table 5, Table 10, Table 18, Table 23, and Table 30.
184 . The method of claim 175 , wherein the one or more methylation sites are one or more methylation sites of Table 5.
185 . The method of claim 175 , wherein the one or more methylation sites are 2 or more methylation sites of Table 5.
186 . The method of claim 175 , wherein the one or more methylation sites are 3 or more methylation sites of Table 5.
187 . The method of claim 175 , wherein the one or more methylation sites are 4 or more methylation sites of Table 5.
188 . The method of claim 175 , wherein the one or more methylation sites are 5 or more methylation sites of Table 5.
189 . The method of claim 175 , wherein the one or more methylation sites are 10 or more methylation sites of Table 5.
190 . The method of claim 175 , wherein the one or more methylation sites are all of the methylation sites of Table 5.
191 . The method of claim 175 , wherein the one or more methylation sites are one or more methylation sites of Table 10.
192 . The method of claim 175 , wherein the one or more methylation sites are 2 or more methylation sites of Table 10.
193 . The method of claim 175 , wherein the one or more methylation sites are 3 or more methylation sites of Table 10.
194 . The method of claim 175 , wherein the one or more methylation sites are 4 or more methylation sites of Table 10.
195 . The method of claim 175 , wherein the one or more methylation sites are 5 or more methylation sites of Table 10.
196 . The method of claim 175 , wherein the one or more methylation sites are 10 or more methylation sites of Table 10.
197 . The method of claim 175 , wherein the one or more methylation sites are all of the methylation sites of Table 10.
198 . The method of claim 175 , wherein the one or more methylation sites are one or more methylation sites of Table 18.
199 . The method of claim 175 , wherein the one or more methylation sites are 2 or more methylation sites of Table 18.
200 . The method of claim 175 , wherein the one or more methylation sites are 3 or more methylation sites of Table 18.
201 . The method of claim 175 , wherein the one or more methylation sites are 4 or more methylation sites of Table 18.
202 . The method of claim 175 , wherein the one or more methylation sites are 5 or more methylation sites of Table 18.
203 . The method of claim 175 , wherein the one or more methylation sites are 10 or more methylation sites of Table 18.
204 . The method of claim 175 , wherein the one or more methylation sites are all of the methylation sites of Table 18.
205 . The method of claim 175 , wherein the one or more methylation sites are one or more methylation sites of Table 23.
206 . The method of claim 175 , wherein the one or more methylation sites are 2 or more methylation sites of Table 23.
207 . The method of claim 175 , wherein the one or more methylation sites are 3 or more methylation sites of Table 23.
208 . The method of claim 175 , wherein the one or more methylation sites are 4 or more methylation sites of Table 23.
209 . The method of claim 175 , wherein the one or more methylation sites are 5 or more methylation sites of Table 23.
210 . The method of claim 175 , wherein the one or more methylation sites are 10 or more methylation sites of Table 23.
211 . The method of claim 175 , wherein the one or more methylation sites are all of the methylation sites of Table 23.
212 . The method of claim 175 , wherein the one or more methylation sites are one or more methylation sites of Table 30.
213 . The method of claim 175 , wherein the one or more methylation sites are 2 or more methylation sites of Table 30.
214 . The method of claim 175 , wherein the one or more methylation sites are 3 or more methylation sites of Table 30.
215 . The method of claim 175 , wherein the one or more methylation sites are 4 or more methylation sites of Table 30.
216 . The method of claim 175 , wherein the one or more methylation sites are 5 or more methylation sites of Table 30.
217 . The method of claim 175 , wherein the one or more methylation sites are 10 or more methylation sites of Table 30.
218 . The method of claim 175 , wherein the one or more methylation sites are all of the methylation sites of Table 30.
219 . The method of any of claims 175 - 218 , wherein the tumor DNA is ctDNA.
220 . The method of any of claims 175 - 219 , wherein the immunotherapy is an immune checkpoint inhibitor therapy.
221 . The method of any of claims 175 - 220 , further comprising administering to the subject an additional cancer therapy.
222 . The method of claim 221 , wherein the additional cancer therapy comprises chemotherapy, radiotherapy, immunotherapy, or a combination thereof.
223 . The method of any of claims 175 - 222 , wherein the subject was previously treated for SCLC.
224 . The method of claim 223 , wherein the subject was resistant to the previous treatment.
225 . The method of any of claims 175 - 224 , wherein the subject was determined to have SCLC-I based on the analysis of the tumor DNA.
226 . The method of any of claims 175 - 225 , wherein the subject was further determined, from the analysis of the tumor DNA from the subject, to have differential methylation of one or more methylation sites of Table 13 compared to the reference or control sample.
227 . The method of any of claims 175 - 226 , wherein the reference or control sample is a DNA sample obtained from healthy cells from the subject.
228 . The method of any of claims 175 - 226 , wherein the reference or control sample is a DNA sample obtained from healthy cells from a reference subject.
229 . A method for classifying a subject having small cell lung cancer (SCLC), the method comprising:
(a) determining, from DNA from the subject, a methylation status of one or more methylation sites selected from the methylation sites of Tables 1-10, 15-18, 20-23, and 27-30; and (b) classifying the subject as having SCLC-A, SCLC-N, SCLC-P, or SCLC-I based on the methylation status of the one or more methylation sites.
230 . The method of claim 229 , wherein (b) comprises classifying the subject as having SCLC-A.
231 . The method of claim 230 , wherein the one or more methylation sites are one or more methylation sites selected from the methylation sites of Table 2, Table 7, Table 15, Table 20, and Table 27.
232 . The method of claim 230 , wherein the one or more methylation sites are 2 or more methylation sites selected from the methylation sites of Table 2, Table 7, Table 15, Table 20, and Table 27.
233 . The method of claim 230 , wherein the one or more methylation sites are 3 or more methylation sites selected from the methylation sites of Table 2, Table 7, Table 15, Table 20, and Table 27.
234 . The method of claim 230 , wherein the one or more methylation sites are 4 or more methylation sites selected from the methylation sites of Table 2, Table 7, Table 15, Table 20, and Table 27.
235 . The method of claim 232 , wherein the one or more methylation sites are 5 or more methylation sites selected from the methyation sites of Table 2, Table 7, Table 15, Table 20, and Table 27.
236 . The method of claim 232 , wherein the one or more methylation sites are 10 or more methylation sites selected from the methyation sites of Table 2, Table 7, Table 15, Table 20, and Table 27.
237 . The method of claim 232 , wherein the one or more methylation sites are twenty or more methylation sites selected from the methyation sites of Table 2, Table 7, Table 15, Table 20, and Table 27.
238 . The method of claim 232 , wherein the one or more methylation sites are fifty or more methylation sites selected from the methyation sites of Table 2, Table 7, Table 15, Table 20, and Table 27.
239 . The method of claim 230 , wherein the one or more methylation sites are one or more methylation sites of Table 2.
240 . The method of claim 230 , wherein the one or more methylation sites are 2 or more methylation sites of Table 2.
241 . The method of claim 230 , wherein the one or more methylation sites are 3 or more methylation sites of Table 2.
242 . The method of claim 230 , wherein the one or more methylation sites are 4 or more methylation sites of Table 2.
243 . The method of claim 230 , wherein the one or more methylation sites are 5 or more methylation sites of Table 2.
244 . The method of claim 230 , wherein the one or more methylation sites are 10 or more methylation sites of Table 2.
245 . The method of claim 230 , wherein the one or more methylation sites are all of the methylation sites of Table 2.
246 . The method of claim 230 , wherein the one or more methylation sites are one or more methylation sites of Table 7.
247 . The method of claim 230 , wherein the one or more methylation sites are 2 or more methylation sites of Table 7.
248 . The method of claim 230 , wherein the one or more methylation sites are 3 or more methylation sites of Table 7.
249 . The method of claim 230 , wherein the one or more methylation sites are 4 or more methylation sites of Table 7.
250 . The method of claim 230 , wherein the one or more methylation sites are 5 or more methylation sites of Table 7.
251 . The method of claim 230 , wherein the one or more methylation sites are 10 or more methylation sites of Table 7.
252 . The method of claim 230 , wherein the one or more methylation sites are all of the methylation sites of Table 7.
253 . The method of claim 230 , wherein the one or more methylation sites are one or more methylation sites of Table 15.
254 . The method of claim 230 , wherein the one or more methylation sites are 2 or more methylation sites of Table 15.
255 . The method of claim 230 , wherein the one or more methylation sites are 3 or more methylation sites of Table 15.
256 . The method of claim 230 , wherein the one or more methylation sites are 4 or more methylation sites of Table 15.
257 . The method of claim 230 , wherein the one or more methylation sites are 5 or more methylation sites of Table 15.
258 . The method of claim 230 , wherein the one or more methylation sites are 10 or more methylation sites of Table 15.
259 . The method of claim 230 , wherein the one or more methylation sites are all of the methylation sites of Table 15.
260 . The method of claim 230 , wherein the one or more methylation sites are one or more methylation sites of Table 20.
261 . The method of claim 230 , wherein the one or more methylation sites are 2 or more methylation sites of Table 20.
262 . The method of claim 230 , wherein the one or more methylation sites are 3 or more methylation sites of Table 20.
263 . The method of claim 230 , wherein the one or more methylation sites are 4 or more methylation sites of Table 20.
264 . The method of claim 230 , wherein the one or more methylation sites are 5 or more methylation sites of Table 20.
265 . The method of claim 230 , wherein the one or more methylation sites are 10 or more methylation sites of Table 20.
266 . The method of claim 230 , wherein the one or more methylation sites are all of the methylation sites of Table 20.
267 . The method of claim 230 , wherein the one or more methylation sites are one or more methylation sites of Table 27.
268 . The method of claim 230 , wherein the one or more methylation sites are 2 or more methylation sites of Table 27.
269 . The method of claim 230 , wherein the one or more methylation sites are 3 or more methylation sites of Table 27.
270 . The method of claim 230 , wherein the one or more methylation sites are 4 or more methylation sites of Table 27.
271 . The method of claim 230 , wherein the one or more methylation sites are 50 or more methylation sites of Table 27.
272 . The method of claim 230 , wherein the one or more methylation sites are 10 or more methylation sites of Table 27.
273 . The method of claim 230 , wherein the one or more methylation sites are all of the methylation sites of Table 27.
274 . The method of any of claims 230 - 273 , further comprising administering to the subject a therapeutically effective amount of a BCL2 inhibitor.
275 . The method of claim 274 , wherein the BCL2 inhibitor is ABT-737 or navitoclax.
276 . The method of any of claims 230 - 274 , further comprising administering to the subject a therapeutically effective amount of a DLL3-targeted therapeutic.
277 . The method of claim 276 , wherein the DLL3-targeted therapeutic comprises an anti-DLL3 antibody or fragment thereof.
278 . The method of claim 277 , wherein the anti-DLL3 antibody or fragment thereof is rovalpituzumab.
279 . The method of claim 276 , wherein the DLL3-targeted therapeutic is an antibody-drug conjugate.
280 . The method of claim 279 , wherein the antibody-drug conjugate is rovalpituzumab tesirine.
281 . The method of claim 229 , wherein (b) comprises classifying the subject as having SCLC-N.
282 . The method of claim 281 , wherein the one or more methylation sites are one or more methylation sites selected from the methyation sites of Table 3, Table 8, Table 16, Table 21, and Table 28.
283 . The method of claim 281 , wherein the one or more methylation sites are 2 or more methylation sites selected from the methyation sites of Table 3, Table 8, Table 16, Table 21, and Table 28.
284 . The method of claim 281 , wherein the one or more methylation sites are 3 or more methylation sites selected from the methyation sites of Table 3, Table 8, Table 16, Table 21, and Table 28.
285 . The method of claim 281 , wherein the one or more methylation sites are 4 or more methylation sites selected from the methyation sites of Table 3, Table 8, Table 16, Table 21, and Table 28.
286 . The method of claim 281 , wherein the one or more methylation sites are 5 or more methylation sites selected from the methyation sites of Table 3, Table 8, Table 16, Table 21, and Table 28.
287 . The method of claim 281 , wherein the one or more methylation sites are 10 or more methylation sites selected from the methyation sites of Table 3, Table 8, Table 16, Table 21, and Table 28.
288 . The method of claim 281 , wherein the one or more methylation sites are twenty or more methylation sites selected from the methyation sites of Table 3, Table 8, Table 16, Table 21, and Table 28.
289 . The method of claim 281 , wherein the one or more methylation sites are fifty or more methylation sites selected from the methyation sites of Table 3, Table 8, Table 16, Table 21, and Table 28.
290 . The method of claim 281 , wherein the one or more methylation sites are one or more methylation sites of Table 3.
291 . The method of claim 281 , wherein the one or more methylation sites are 2 or more methylation sites of Table 3.
292 . The method of claim 281 , wherein the one or more methylation sites are 3 or more methylation sites of Table 3.
293 . The method of claim 281 , wherein the one or more methylation sites are 4 or more methylation sites of Table 3.
294 . The method of claim 281 , wherein the one or more methylation sites are 5 or more methylation sites of Table 3.
295 . The method of claim 281 , wherein the one or more methylation sites are 10 or more methylation sites of Table 3.
296 . The method of claim 281 , wherein the one or more methylation sites are all of the methylation sites of Table 3.
297 . The method of claim 281 , wherein the one or more methylation sites are one or more methylation sites of Table 8.
298 . The method of claim 281 , wherein the one or more methylation sites are 2 or more methylation sites of Table 8.
299 . The method of claim 281 , wherein the one or more methylation sites are 3 or more methylation sites of Table 8.
300 . The method of claim 281 , wherein the one or more methylation sites are 4 or more methylation sites of Table 8.
301 . The method of claim 281 , wherein the one or more methylation sites are 5 or more methylation sites of Table 8.
302 . The method of claim 281 , wherein the one or more methylation sites are 10 or more methylation sites of Table 8.
303 . The method of claim 281 , wherein the one or more methylation sites are all of the methylation sites of Table 8.
304 . The method of claim 281 , wherein the one or more methylation sites are one or more methylation sites of Table 16.
305 . The method of claim 281 , wherein the one or more methylation sites are 2 or more methylation sites of Table 16.
306 . The method of claim 281 , wherein the one or more methylation sites are 3 or more methylation sites of Table 16.
307 . The method of claim 281 , wherein the one or more methylation sites are 4 or more methylation sites of Table 16.
308 . The method of claim 281 , wherein the one or more methylation sites are 5 or more methylation sites of Table 16.
309 . The method of claim 281 , wherein the one or more methylation sites are 10 or more methylation sites of Table 16.
310 . The method of claim 281 , wherein the one or more methylation sites are all of the methylation sites of Table 16.
311 . The method of claim 281 , wherein the one or more methylation sites are one or more methylation sites of Table 21.
312 . The method of claim 281 , wherein the one or more methylation sites are 2 or more methylation sites of Table 21.
313 . The method of claim 281 , wherein the one or more methylation sites are 3 or more methylation sites of Table 21.
314 . The method of claim 281 , wherein the one or more methylation sites are 4 or more methylation sites of Table 21.
315 . The method of claim 281 , wherein the one or more methylation sites are 5 or more methylation sites of Table 21.
316 . The method of claim 281 , wherein the one or more methylation sites are 10 or more methylation sites of Table 21.
317 . The method of claim 281 , wherein the one or more methylation sites are all of the methylation sites of Table 21.
318 . The method of claim 281 , wherein the one or more methylation sites are one or more methylation sites of Table 28.
319 . The method of claim 281 , wherein the one or more methylation sites are 2 or more methylation sites of Table 28.
320 . The method of claim 281 , wherein the one or more methylation sites are 3 or more methylation sites of Table 28.
321 . The method of claim 281 , wherein the one or more methylation sites are 4 or more methylation sites of Table 28.
322 . The method of claim 281 , wherein the one or more methylation sites are 5 or more methylation sites of Table 28.
323 . The method of claim 281 , wherein the one or more methylation sites are 10 or more methylation sites of Table 28.
324 . The method of claim 281 , wherein the one or more methylation sites are all of the methylation sites of Table 28.
325 . The method of claim 281 - 324 , further comprising administering to the subject a therapeutically effective amount of an AURK inhibitor.
326 . The method of claim 325 , wherein the AURK inhibitor is CYC-116, alisertib, or AS-703569.
327 . The method of claim 229 , wherein (b) comprises classifying the subject as having SCLC-P.
328 . The method of claim 327 , wherein the one or more methylation sites are one or more methylation sites selected from the methyation sites of Table 4, Table 9, Table 17, Table 22, and Table 29.
329 . The method of claim 327 , wherein the one or more methylation sites are 2 or more methylation sites selected from the methyation sites of Table 4, Table 9, Table 17, Table 22, and Table 29.
330 . The method of claim 327 , wherein the one or more methylation sites are 3 or more methylation sites selected from the methyation sites of Table 4, Table 9, Table 17, Table 22, and Table 29.
331 . The method of claim 327 , wherein the one or more methylation sites are 4 or more methylation sites selected from the methyation sites of Table 4, Table 9, Table 17, Table 22, and Table 29.
332 . The method of claim 327 , wherein the one or more methylation sites are 5 or more methylation sites selected from the methyation sites of Table 4, Table 9, Table 17, Table 22, and Table 29.
333 . The method of claim 327 , wherein the one or more methylation sites are 10 or more methylation sites selected from the methyation sites of Table 4, Table 9, Table 17, Table 22, and Table 29.
334 . The method of claim 327 , wherein the one or more methylation sites are twenty or more methylation sites selected from the methyation sites of Table 4, Table 9, Table 17, Table 22, and Table 29.
335 . The method of claim 327 , wherein the one or more methylation sites are fifty or more methylation sites selected from the methyation sites of Table 4, Table 9, Table 17, Table 22, and Table 29.
336 . The method of claim 327 , wherein the one or more methylation sites are one or more methylation sites of Table 4.
337 . The method of claim 327 , wherein the one or more methylation sites are 2 or more methylation sites of Table 4.
338 . The method of claim 327 , wherein the one or more methylation sites are three or more methylation sites of Table 4.
339 . The method of claim 327 , wherein the one or more methylation sites are 4 or more methylation sites of Table 4.
340 . The method of claim 327 , wherein the one or more methylation sites are 5 or more methylation sites of Table 4.
341 . The method of claim 327 , wherein the one or more methylation sites are 10 or more methylation sites of Table 4.
342 . The method of claim 327 , wherein the one or more methylation sites are all of the methylation sites of Table 4.
343 . The method of claim 327 , wherein the one or more methylation sites are one or more methylation sites of Table 9.
344 . The method of claim 327 , wherein the one or more methylation sites are 2 or more methylation sites of Table 9.
345 . The method of claim 327 , wherein the one or more methylation sites are 3 or more methylation sites of Table 9.
346 . The method of claim 327 , wherein the one or more methylation sites are 4 or more methylation sites of Table 9.
347 . The method of claim 327 , wherein the one or more methylation sites are 5 or more methylation sites of Table 9.
348 . The method of claim 327 , wherein the one or more methylation sites are 10 or more methylation sites of Table 9.
349 . The method of claim 327 , wherein the one or more methylation sites are all of the methylation sites of Table 9.
350 . The method of claim 327 , wherein the one or more methylation sites are one or more methylation sites of Table 17.
351 . The method of claim 327 , wherein the one or more methylation sites are 2 or more methylation sites of Table 17.
352 . The method of claim 327 , wherein the one or more methylation sites are 3 or more methylation sites of Table 17.
353 . The method of claim 327 , wherein the one or more methylation sites are 4 or more methylation sites of Table 17.
354 . The method of claim 327 , wherein the one or more methylation sites are 5 or more methylation sites of Table 17.
355 . The method of claim 327 , wherein the one or more methylation sites are 10 or more methylation sites of Table 17.
356 . The method of claim 327 , wherein the one or more methylation sites are all of the methylation sites of Table 17.
357 . The method of claim 327 , wherein the one or more methylation sites are one or more methylation sites of Table 22.
358 . The method of claim 327 , wherein the one or more methylation sites are 2 or more methylation sites of Table 22.
359 . The method of claim 327 , wherein the one or more methylation sites are 3 or more methylation sites of Table 22.
360 . The method of claim 327 , wherein the one or more methylation sites are 4 or more methylation sites of Table 22.
361 . The method of claim 327 , wherein the one or more methylation sites are 5 or more methylation sites of Table 22.
362 . The method of claim 327 , wherein the one or more methylation sites are 10 or more methylation sites of Table 22.
363 . The method of claim 327 , wherein the one or more methylation sites are all of the methylation sites of Table 22.
364 . The method of claim 327 , wherein the one or more methylation sites are one or more methylation sites of Table 29.
365 . The method of claim 327 , wherein the one or more methylation sites are 2 or more methylation sites of Table 29.
366 . The method of claim 327 , wherein the one or more methylation sites are 3 or more methylation sites of Table 29.
367 . The method of claim 327 , wherein the one or more methylation sites are 4 or more methylation sites of Table 29.
368 . The method of claim 327 , wherein the one or more methylation sites are 5 or more methylation sites of Table 29.
369 . The method of claim 327 , wherein the one or more methylation sites are 10 or more methylation sites of Table 29.
370 . The method of claim 327 , wherein the one or more methylation sites are all of the methylation sites of Table 29.
371 . The method of any of claims 327 - 370 , further comprising administering to the subject a therapeutically effective amount of a platinum-containing chemotherapeutic agent.
372 . The method of claim 371 , wherein the platinum-containing chemotherapeutic agent is cisplatin, carboplatin, oxaliplatin, nedaplatin, picoplatin, or satraplatin.
373 . The method of any of claims 327 - 349 , further comprising administering to the subject a therapeutically effective amount of a PARP inhibitor.
374 . The method of claim 373 , wherein the PARP inhibitor is talazoparib, olaparib, niraparib, AZD-2461, or rucaparib.
375 . The method of any of claims 327 - 349 , further comprising administering to the subject a therapeutically effective amount of an anti-metabolite.
376 . The method of claim 375 , wherein the anti-metabolite is pemetrexed, methotrexate, or pralatrexate.
377 . The method of any of claims 327 - 349 , further comprising administering to the subject a therapeutically effective amount of a nucleoside analog.
378 . The method of claim 377 , wherein the nucleoside analog is floxuridine, cytarabine, clofarabine, or fludarabine.
379 . The method of claim 229 , wherein (b) comprises classifying the subject as having SCLC-I.
380 . The method of claim 379 , wherein the one or more methylation sites are one or more methylation sites selected from the methyation sites of Table 5, Table 10, Table 18, Table 23, and Table 30.
381 . The method of claim 379 , wherein the one or more methylation sites are 2 or more methylation sites selected from the methyation sites of Table 5, Table 10, Table 18, Table 23, and Table 30.
382 . The method of claim 379 , wherein the one or more methylation sites are 3 or more methylation sites selected from the methyation sites of Table 5, Table 10, Table 18, Table 23, and Table 30.
383 . The method of claim 379 , wherein the one or more methylation sites are 4 or more methylation sites selected from the methyation sites of Table 5, Table 10, Table 18, Table 23, and Table 30.
384 . The method of claim 379 , wherein the one or more methylation sites are 5 or more methylation sites selected from the methyation sites of Table 5, Table 10, Table 18, Table 23, and Table 30.
385 . The method of claim 379 , wherein the one or more methylation sites are 10 or more methylation sites selected from the methyation sites of Table 5, Table 10, Table 18, Table 23, and Table 30.
386 . The method of claim 379 , wherein the one or more methylation sites are twenty or more methylation sites selected from the methyation sites of Table 5, Table 10, Table 18, Table 23, and Table 30.
387 . The method of claim 379 , wherein the one or more methylation sites are fifty or more methylation sites selected from the methyation sites of Table 5, Table 10, Table 18, Table 23, and Table 30.
388 . The method of claim 379 , wherein the one or more methylation sites are one or more methylation sites of Table 5.
389 . The method of claim 379 , wherein the one or more methylation sites are 2 or more methylation sites of Table 5.
390 . The method of claim 379 , wherein the one or more methylation sites are 3 or more methylation sites of Table 5.
391 . The method of claim 379 , wherein the one or more methylation sites are 4 or more methylation sites of Table 5.
392 . The method of claim 379 , wherein the one or more methylation sites are 5 or more methylation sites of Table 5.
393 . The method of claim 379 , wherein the one or more methylation sites are 10 or more methylation sites of Table 5.
394 . The method of claim 379 , wherein the one or more methylation sites are all of the methylation sites of Table 5.
395 . The method of claim 379 , wherein the one or more methylation sites are one or more methylation sites of Table 10.
396 . The method of claim 379 , wherein the one or more methylation sites are 2 or more methylation sites of Table 10.
397 . The method of claim 379 , wherein the one or more methylation sites are 3 or more methylation sites of Table 10.
398 . The method of claim 379 , wherein the one or more methylation sites are 4 or more methylation sites of Table 10.
399 . The method of claim 379 , wherein the one or more methylation sites are 5 or more methylation sites of Table 10.
400 . The method of claim 379 , wherein the one or more methylation sites are 10 or more methylation sites of Table 10.
401 . The method of claim 379 , wherein the one or more methylation sites are all of the methylation sites of Table 10.
402 . The method of claim 379 , wherein the one or more methylation sites are one or more methylation sites of Table 18.
403 . The method of claim 379 , wherein the one or more methylation sites are 2 or more methylation sites of Table 18.
404 . The method of claim 379 , wherein the one or more methylation sites are 3 or more methylation sites of Table 18.
405 . The method of claim 379 , wherein the one or more methylation sites are 4 or more methylation sites of Table 18.
406 . The method of claim 379 , wherein the one or more methylation sites are 5 or more methylation sites of Table 18.
407 . The method of claim 379 , wherein the one or more methylation sites are 10 or more methylation sites of Table 18.
408 . The method of claim 379 , wherein the one or more methylation sites are all of the methylation sites of Table 18.
409 . The method of claim 379 , wherein the one or more methylation sites are one or more methylation sites of Table 23.
410 . The method of claim 379 , wherein the one or more methylation sites are 2 or more methylation sites of Table 23.
411 . The method of claim 379 , wherein the one or more methylation sites are 3 or more methylation sites of Table 23.
412 . The method of claim 379 , wherein the one or more methylation sites are 4 or more methylation sites of Table 23.
413 . The method of claim 379 , wherein the one or more methylation sites are 5 or more methylation sites of Table 23.
414 . The method of claim 379 , wherein the one or more methylation sites are 10 or more methylation sites of Table 23.
415 . The method of claim 379 , wherein the one or more methylation sites are all of the methylation sites of Table 23.
416 . The method of claim 379 , wherein the one or more methylation sites are one or more methylation sites of Table 30.
417 . The method of claim 379 , wherein the one or more methylation sites are 2 or more methylation sites of Table 30.
418 . The method of claim 379 , wherein the one or more methylation sites are 3 or more methylation sites of Table 30.
419 . The method of claim 379 , wherein the one or more methylation sites are 4 or more methylation sites of Table 30.
420 . The method of claim 379 , wherein the one or more methylation sites are 5 or more methylation sites of Table 30.
421 . The method of claim 379 , wherein the one or more methylation sites are 10 or more methylation sites of Table 30.
422 . The method of claim 379 , wherein the one or more methylation sites are all of the methylation sites of Table 30.
423 . The method of any of claims 379 - 422 , further comprising administering to the subject a therapeutically effective amount of an immunotherapy.
424 . The method of claim 423 , wherein the immunotherapy is a checkpoint blockade therapy.
425 . The method of any of claims 379 - 401 , further comprising administering to the subject a therapeutically effective amount of a BTK inhibitor.
426 . The method of claim 425 , wherein the BTK inhibitor is ibrutinib.
427 . The method of any of claims 229 - 426 , wherein the DNA is obtained from blood or plasma from the subject.
428 . The method of any of claims 229 - 427 , wherein the DNA is circulating tumor DNA (ctDNA).
429 . The method of any of claims 229 - 426 , wherein the DNA is obtained from cancer tissue from the subject.
430 . The method of any of claims 229 - 429 , further comprising determining, from the DNA from the subject, a methylation status of one or more methylation sites of Table 13.
431 . The method of claim 430 , wherein the one or more methylation sites are one or more methylation sites of Table 13.
432 . The method of claim 430 , wherein the one or more methylation sites are 5 or more methylation sites of Table 13.
433 . A method of identifying a subject with cancer as having SCLC, the method comprising:
(a) determining, from DNA from the subject, a methylation status of one or more methylation sites of Table 13; and (b) identifying the subject as having SCLC based on the methylation status of the one or more methylation sites.
434 . The method of claim 433 , wherein the one or more methylation sites are 2 or more methylation sites of Table 13.
435 . The method of claim 433 , wherein the one or more methylation sites are 5 or more methylation sites of Table 13.
436 . The method of claim 433 , wherein the one or more methylation sites are 10 or more methylation sites of Table 13.
437 . The method of claim 433 , wherein the one or more methylation sites are twenty or more methylation sites of Table 13.
438 . The method of claim 433 , wherein the one or more methylation sites are all of the methylation sites of Table 13.
439 . The method of any of claims 433 - 438 , wherein the DNA is obtained from blood or plasma from the subject.
440 . The method of any of claims 433 - 439 , wherein the DNA is ctDNA.
441 . The method of any of claims 433 - 438 , wherein the DNA is obtained from cancer tissue from the subject.
442 . The method of any of claims 433 - 441 , further comprising treating the subject for SCLC.
443 . A method for treating a subject for SCLC comprising administering an SCLC therapy to a subject determined, from analysis of tumor DNA from the subject, to have differential methylation at one or more methylation sites of Table 13 compared to a reference or control sample.
444 . The method of claim 443 , wherein the SCLC therapy comprises chemotherapy, immunotherapy, radiotherapy, or a combination thereof.
445 . The method of claim 443 or 444 , wherein the SCLC therapy comprises a platinum-containing chemotherapeutic agent.
446 . The method of claim 445 , wherein the platinum-containing chemotherapeutic agent is cisplatin, carboplatin, oxaliplatin, nedaplatin, picoplatin, or satraplatin.
447 . The method of any of claims 443 - 446 , wherein the one or more methylation sites are 2 or more methylation sites of Table 13.
448 . The method of any of claims 443 - 446 , wherein the one or more methylation sites are 5 or more methylation sites of Table 13.
449 . A method of evaluating tumor burden in a subject having SCLC, the method comprising determining, from DNA from the subject, a methylation status of one or more methylation sites of Table 24.
450 . The method of claim 449 , wherein the one or more methylation sites are 2 or more methylation sites of Table 24.
451 . The method of claim 449 , wherein the one or more methylation sites are 3 or more methylation sites of Table 24.
452 . The method of claim 449 , wherein the one or more methylation sites are 4 or more methylation sites of Table 24.
453 . The method of claim 449 , wherein the one or more methylation sites are 5 or more methylation sites of Table 24.
454 . The method of claim 449 , wherein the one or more methylation sites are 10 or more methylation sites of Table 24.
455 . The method of claim 449 , wherein the one or more methylation sites are twenty or more methylation sites of Table 24.
456 . The method of claim 449 , wherein the one or more methylation sites are all of the methylation sites of Table 24.
457 . The method of any of claims 449 - 456 , wherein the DNA is obtained from blood or plasma from the subject.
458 . The method of any of claims 449 - 456 , wherein the DNA is ctDNA.
459 . The method of any of claims 449 - 456 , wherein the DNA is obtained from cancer tissue from the subject.
460 . A method for determining a response of a subject having SCLC to a cancer therapy, the method comprising determining, from DNA from the subject, a methylation status of one or more methylation sites of Table 24.
461 . The method of claim 460 , wherein the one or more methylation sites are 2 or more methylation sites of Table 24.
462 . The method of claim 460 , wherein the one or more methylation sites are 3 or more methylation sites of Table 24.
463 . The method of claim 460 , wherein the one or more methylation sites are 5 or more methylation sites of Table 24.
464 . The method of claim 460 , wherein the one or more methylation sites are 10 or more methylation sites of Table 24.
465 . The method of claim 460 , wherein the one or more methylation sites are twenty or more methylation sites of Table 24.
466 . The method of claim 460 , wherein the one or more methylation sites are all of the methylation sites of Table 24.
467 . The method of any of claims 460 - 466 , wherein the DNA is obtained from blood or plasma from the subject.
468 . The method of any of claims 460 - 466 , wherein the DNA is ctDNA.
469 . The method of any of claims 460 - 466 , wherein the DNA is obtained from cancer tissue from the subject.
470 . A method for treating a subject having SCLC, the method comprising:
(a) determining, from DNA from the subject, a methylation level of one or more methylation sites of Table 24; (b) administering a dose of a first cancer therapy to the subject; (c) determining, from DNA from the subject, an additional methylation level of the one or more methylation sites of Table 24; and if the additional methylation level is not increased compared with the methylation level, administering an additional dose of the first cancer therapy to the subject: or if the additional methylation level is increased compared with the methylation level, administering to the subject a second cancer therapy that is different from the first cancer therapy.
471 . The method of claim 470 , wherein the one or more methylation sites are 2 or more methylation sites of Table 24.
472 . The method of claim 470 , wherein the one or more methylation sites are 3 or more methylation sites of Table 24.
473 . The method of claim 470 , wherein the one or more methylation sites are 5 or more methylation sites of Table 24.
474 . The method of claim 470 , wherein the one or more methylation sites are 10 or more methylation sites of Table 24.
475 . The method of claim 470 , wherein the one or more methylation sites are twenty or more methylation sites of Table 24.
476 . The method of claim 470 , wherein the one or more methylation sites are all of the methylation sites of Table 24.
477 . The method of any of claims 470 - 476 , wherein the DNA is obtained from blood or plasma from the subject.
478 . The method of any of claims 470 - 476 , wherein the DNA is ctDNA.
479 . The method of any of claims 470 - 476 , wherein the DNA is obtained from cancer tissue from the subject.
480 . The method of any of claims 470 - 479 , wherein the method comprises administering an additional dose of the cancer therapy to the subject if the additional methylation level is reduced compared with the methylation level.
481 . The method of claim 480 , wherein the method comprises administering the additional dose of the cancer therapy to the subject if the additional methylation level is reduced by at least 10% compared with the methylation level.
482 . The method of claim 481 , wherein the method comprises administering the additional dose of the cancer therapy to the subject if the additional methylation level is reduced by at least 20% compared with the methylation level.Join the waitlist — get patent alerts
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